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Biomedical subjects

J A Lyon

Publications and source records attributed to J A Lyon.

51 records · Page 3Linked to original sources
PubMed1984

Localization of the major Plasmodium falciparum glycoprotein on the surface of mature intraerythrocytic trophozoites and schizonts.

The subcellular location of the major malarial glycoprotein in erythrocytes infected with schizonts of Plasmodium falciparum has been studied by two methods. In the first, glycoproteins were labelled with [3H]glucosamine or [3H]isoleucine during in vitro culture. Trypsin treatment of intact infected erythrocytes caused no major qualitative or quantitative changes in [3H]glucosamine labelled glycoproteins or [3H]isoleucine labelled proteins separated by sodium dodecylsulfate polyacrylamide gel electrophoresis. However, in the presence of Triton X-100 the labelled glycoproteins and proteins were completely cleaved by trypsin. In the second method, two monoclonal antibodies which specifically immunoprecipitate the major 195 kDa glycoprotein failed to react on indirect immunofluorescence with intact non-fixed schizont-infected erythrocytes, but reacted strongly with saponin released schizonts indicating specificity for the surface of mature intracellular parasites. Immunoelectronmicroscopy using ferritin-conjugated secondary antibody confirmed the location of the epitope(s) recognized by these monoclonals on the surface of intracellular parasites. Ferritin particles were not associated with knob-bearing erythrocyte membranes. The results indicate that only a small proportion or none of the 195 kDa glycoprotein is on the surface of the infected erythrocyte and that the largest proportion is expressed on the surface of mature intraerythrocytic parasites.

Animals↗
PubMed1983

Cefoperazone (Cefobid, Pfizer).

Cefoperazone is a new beta-lactam antibiotic that possesses a broad spectrum of activity against gram-positive and gram-negative organisms. Cefoperazone differs from all previous cephalosporins in that it has exceptional activity against P. aeruginosa. The other distinguishing feature of cefoperazone is its high rate of biliary excretion, which will allow for treatment of biliary tract infections. Renal elimination accounts for only 20 percent of the agent's elimination; dosage modification is not necessary in decreased renal function. The clinical response rate of infections to cefoperazone is similar to that of moxalactam, cefotaxime, or the cephalosporins in general. The overall incidence of side effects was 14 percent in U.S. trials, with skin rash, fever, or urticaria occurring in 1 percent; phlebitis and injection-site pain in 2 percent; and diarrhea in 5 percent. As with the other third-generation cephalosporins, cefoperazone requires close scrutiny because of its expected high cost and the lack of comparative trials with standard antibiotic regimens.

Bacterial Infections↗
PubMed1982

Membrane lipid composition modulates the binding specificity of a monoclonal antibody against liposomes.

A hybridoma secreting a monoclonal IgM 'anti-liposome' antibody was produced after injecting a mouse with liposomes containing dipalmitoylphosphatidylcholine, cholesterol, dicetyl phosphate, and lipid A. The antibody was selected by assaying for complement-dependent damage to liposomes lacking lipid A. The monoclonal antibody reacted best with liposomes containing the original immunizing mixture of lipids. Deletion of individual lipid constituents from liposomes diminished the ability of the liposomes to bind (adsorb) the antibody. Binding of the antibody was enhanced by including lipid A or galactosylceramide in the lipid bilayer, or by substituting egg phosphatidylcholine for dimyristoyl- (or dipalmitoyl-) phosphatidylcholine. Sphingomyelin could be substituted for dimyristoylphosphatidylcholine without altering the adsorption of antibody. Although the monoclonal anti-liposome antibody was completely inhibited by phosphocholine, it was probably not a conventional anti-phosphocholine antibody. The antibody apparently had a partial specificity for phosphate, and was inhibited by glycerophosphocholine, glycerophosphate, sodium phosphate, sodium sulfate, and inositol hexaphosphate, but not by choline or inositol.

Animals↗
PubMed1982

Pharmacokinetics of single-dose erythromycin in normal and alcoholic liver disease subjects.

Six normal males and eight male subjects with alcoholic liver disease (ALD) and ascites were given a single 500-mg dose of erythromycin base. Twelve serum samples were collected at 0, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, and 24 h after dosing and assayed microbiologically for erythromycin concentration. Absorption was characterized by a zero-order model for both groups. ALD subjects demonstrated a shorter lag time (2.0 versus 3.0 h), an earlier peak (4.6 versus 6.3 h, P less than 0.05), and higher peak concentrations (2.04 versus 1.50 micrograms/ml) than normal subjects. Previously unreported biphasic elimination kinetics after oral dosing were observed in five and four ALD subjects. In the ALD group, the mean half lives for the first (alpha) and terminal (beta) phases were 1.6 and 4.5 h, respectively, and in normal subjects, were 1.3 and 6.6 h. The difference in alpha between groups was significant, P less than 0.05. The clinical significance of this finding for ALD patients receiving prolonged courses of erythromycin is discussed.

Absorption↗
PubMed1981

Use of monoclonal antibody to immunochemically characterize variant-specific surface coat glycoprotein from Trypanosoma rhodesiense.

Monoclonal antibodies were employed to study the molecular basis for charge heterogeneity in variant-specific surface coat glycoprotein prepared from clone CP3B4 of the Wellcome strain of Trypanosoma rhodesiense. Thirteen hybridomas secreting monoclonal antibodies specific for CP3B4 were obtained by fusing murine plasmacytoma cells to spleen cells from mice immunized with purified surface coat glycoprotein. The clone population of CP3B4 trypanosomes was shown to be homogeneous by means of immunofluorescent assays using culture supernatants from each of the 13 hybridomas. No cross-reactivity was found with other variant antigenic types of the same serodeme. Ascitic fluids were generated from 4 of the hybridomas and th molecular and epitopic specificities of the fluids or their IgG fractions were determined isoelectrofocusing of immunoprecipitates of radioiodinated glycoprotein antigen followed by autoradiography revealed that all 3 major components of the charge heterogeneous CP3B4 surface-coat glycoprotein were immunoprecipitated by each of the 4 monoclonal IgG fractions. Immunofluorescent staining of live trypanosomes was obtained with only one of the 4 ascitic fluids. The results show that charge heterogeneity does not derive from a heterogeneous population of parasites. Furthermore, the data indicate that there are at least 2 different epitopic specificities exhibited by the monoclonal antibodies tested and that each of the 3 charge heterogeneous components of the surface coat glycoprotein contains these epitopes. Charge heterogeneity of CP3B4 surface coat glycoprotein may be attributed to post-translational modification or to limited proteolysis.

Animals↗
PubMed1979

Relationship between spray adhesives and congenital malformations.

Evidence from clinical impressions and laboratory slides that spray adhesive products could have a potentially dangerous mutagenic or teratogenic effect was first reported in 1973. However, similar laboratory slides observed by others revealed no significant difference between chromosomal slides of malformed infants and those of normal children in households whose members were exposed to spray adhesives. Because of opposing opinions, a pilot epidemiologic study was initiated to investigate the association between the use of spray adhesives and congenital malformations. All congenital malformations reported on birth certificates from 1971 through 1974 in Oklahoma County, Oklahoma were used. A normal birth was selected as a matching control for each case. Complete and usable questionnaires regarding 112 malformed subjects and 116 controls, including 56 matched controls, were received. There was a statistical association between malformed subjects and household members using spray adhesives. There appears to be sufficient epidemiologic evidence to reopen the controversy with the appeal for further studies.

Abnormalities, Drug-Induced↗
PubMed1978

A controlled investigation of the pharmacokinetics of gentamicin and tobramycin in obese subjects.

For determination of the best basis on which to calculate dosages of gentamicin or tobramycin to be administered to obese patients, the pharmacokinetics of these drugs were studied in 13 obese subjects and 13 subjects of a normal weight following intravenous infusion of 1 mg/kg. Half-lives, elimination constants, and absolute and relative volumes of distribution were calculated. Concentrations of drug in serum were significantly higher and relative volumes of distribution were significantly lower in obese subjects as compared with controls. However, relative volumes of distribution based on lean body mass of obese subjects were significantly greater than those of normal-weight subjects. These results indicate that gentamicin and tobramycin are distributed less to adipose tissue than to other tissues, but partial distribution to adipose tissue does occur. The mean relative volume of distribution in obese subjects closely approximated that in normal subjects when normalized body mass plus 40% of the adipose mass was used as the total weight in obese subjects.

Anti-Bacterial Agents↗
PubMed1976

Formation of ternary complexes of thymidylate synthetase as followed by absorbance, fluorescence, and circular dichroic spectra and gel electrophoresis.

Ternary complexes of thymidylate synthetase (Form II and Form III), which are composed of the enzyme, 5-fluorodeoxyuridylate, and the natural isomer of methylenetetrahydrofolate, were generated by titrating thymidylate synthetase (Form I) in the presence of 5-fluorodeoxyuridylate with either the enzymatically prepared natural isomer or the chemically prepared racemic mixture of the diastereomers of methylenetetrahydrofolate. Such titrations were monitored by absorption, circular dichroic and fluorescence spectroscopy, and polyacrylamide gel electrophoresis. The results of these investigations suggest that the natural isomer of methylenetetrahydrofolate is primarily involved in the formation of stable ternary complexes with thymidylate synthetase and 5-fluorodeoxyuridylate but that the unnatural isomer of methylenetetrahydrofolate, when present in solution, may compete with the natural isomer by forming relatively weak complexes with the enzyme and the 5-fluorodeoxyuridylate.

Binding Sites↗
PubMedDate not supplied

Treatment of septicemic patients with cefoxitin: pharmacokinetics in renal insufficiency.

Experience with cefoxitin in the treatment of septicemia of diverse etiologies in 11 patients is reviewed. Results of a small study of the pharmacokinetics of cefoxitin in patients with renal insufficiency, which was used as a guideline for determining the dosage of cefoxitin for severely ill patients with renal insufficiency, are included. In addition, a summary of data on file at Merck Sharp and Dohme Research Laboratories (Rahway, New Jersey) that concern 135 bacteremic patients who were treated with cefoxitin and evaluated is presented. Although information derived from septicemic patients is among the most difficult to interpret in regard to the efficacy of an investigational antibiotic, both our experience and the summary of data confirm that cefoxitin is a potent antibiotic suitable for use in septicemic patients when the etiologic agent is susceptible; the data also demonstrate that cefoxitin has a significantly expanded spectrum of activity as compared with that of cephalothin.

Cefoxitin↗
PubMedDate not supplied

Inhibition of nitric oxide induction from avian macrophage cell lines by influenza virus.

The virulent avian influenza virus A/Ty/Ont/7732/66 (H5N9) (Ty/Ont) causes a rapid destruction of lymphoid cells in infected birds. Avian macrophage cell lines, HD11 and MQ-NCSU, support productive replication of Ty/Ont and other influenza viruses. Therefore, the ability of these cell lines to produce nitric oxide (NO), a potentially cytotoxic mediator, in response to infection with Ty/Ont was examined. Although treatment with bacterial lipopolysaccharides (LPS) resulted in high NO levels, infection of macrophages with Ty/Ont resulted in NO levels lower than NO levels in untreated cells. Furthermore, Ty/Ont was able to inhibit the positive response to LPS in cultures simultaneously treated with LPS and virus. However, inactivated influenza virus did not exhibit this inhibitory effect. Different strains of influenza virus varied in their ability to inhibit NO production by the macrophages; this may be related to the level of virus replication in these cells. These data suggest that the ability of the avian macrophage to activate the NO synthesis pathway is seriously impaired by infection with virulent influenza viruses such as Ty/Ont.

Amino Acid Oxidoreductases↗